Retinitis pigmentosa (alternatively referred to herein using its full name or the abbreviation "RP") is a group of human hereditary retinal degenerations which are named for the characteristic intraretinal pigment which appears around the mid-peripheral retina of individuals with RP (Berson, E. L. (1996) PNAS 93:4526-4528). Individuals with RP suffer from degeneration of photoreceptor cells which in turn leads to various clinical features which are common among these individuals. For example, RP results in night blindness, gradual loss of peripheral visual field, and eventual loss of central vision. In typical cases, rod photoreceptors are more severely affected early in the disease, hence the early symptom of night blindness. Later in the disease, cone photoreceptors degenerate. Most cases of RP have no extraocular abnormalities. In a minority of families, however, RP is associated with other disease manifestations such as hearing loss in Usher syndrome, polydactyly, obesity, hypogonadism, mental retardation in Bardet-Biedl syndrome, and cardiac conduction defects in Keams-Sayre syndrome. Dryja, T. P. and Li, T. (1995) Human Mol. Genet. 4:1739-1743.
RP can be inherited by an autosomal dominant, autosomal recessive, X-linked, or digenic mode (Kajiwara, K. et al. (1994) Science 264:1604-1608). Substantial genetic heterogeneity has been observed in this condition, with over 20 loci mapped (Dryja, T. P. and Li, T. (1995) Human Mol. Genet. 4:1739-1743; Daiger, S. P. et al. (1995) Behav. Brain Sci. 18:452-467). Mutations have been identified in seven genes which map to seven different chromosomes (Kajiwara, K. et al. (1994) Science 264:1604-1608; Dryja, T. B. et al. (1990) Nature 343:364-366; Farrar, G. J. et al. (1991) Nature 354::478-480; Kajiwara, K. et al. (1991) Nature 354:480-483; McLaughlin, M. E. et al. (1993) Nature Genet. 4:130-133; Dryja, T. P. et al. (1995) PNAS 92:10177-10181; Huang, S. H. et al. (1995) Nature Genet. 11:468-471; Bascom, R. A. et al. (1995) Human Mol. Genet. 4:1895-1902; Weil, D. et al. (1995) Nature 374-60-61). Four of these genes encode proteins in the rod phototransduction cascade-namely rhodopsin (mapped to chromosomes 3q21-q24 (autosomal dominant, autosomal recessive)), the .alpha. and .beta. subunits of rod cGMP phosphodiesterase (mapped to chromosomes 5q31.2-q34 (autosomal recessive), and 4p16.3 (autosomal recessive), respectively)), and the rod cGMP cation-gated channel protein .alpha. subunit (mapped to chromosome 4p14-q13 (autosomal recessive)) (Berson, E. L. (1996) PNAS 93:4526-4528; Dryja, T. P. and Li, T. (1995) Human Mol. Genet. 4:1739-1743). Two of these genes, peripherin/RDS (mapped to chromosome 6p11.2-p21.1 (autosomal dominant, autosomal recessive)) and rod outer segment membrane protein 1 (mapped to chromosome 11q13 (digenic)), encode proteins involved in maintaining photoreceptor outer segment disc structure (Berson, E. L. (1996) PNAS 93:4526-4528; Dryja, T. P. and Li, T. (1995) Human Mol. Genet. 4:1739-1743). Mutations in the gene encoding myosin VIIa (mapped to chromosome 11q13.5 (autosomal recessive)) have been found in a form of RP with associated profound congenital deafness (Usher syndrome) (Berson, E. L. (1996) PNAS 93:4526-4528; Dryja, T. P. and Li, T. (1995) Human Mol. Genet. 4:1739-1743).
An additional locus for autosomal recessive RP has been mapped on chromosome 6p by linkage analysis (Knowles, J. A., et. al., (1994) Hum. Mol. Genet. 3:1401-1403). This locus is approximately 20 centimorgans telomeric from the previously described peripherin/RDS gene, and thus represents a novel disease locus.